1. Field of the Invention
The present invention relates to a novel microorganism and uses thereof in preparation of antihypercholesterolemic agents. More specifically, it relates to a mutant strain of Penicillium citrinum ATCC 38065, and its use in preparation of compactin.
2. Description of the Related Arts
High blood cholesterol levels are recognized as being one of the main causes of cardiopathy, e.g. cardiac infarction, arteriosclerosis or hyperlipaemia. Cholesterol biosynthesis is greatly reduced by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is a rate controlling enzyme. As a result, considerable research has been undertaken with a view to discover physiologically acceptable substances which are capable of inhibiting cholesterol biosynthesis and thus are capable of reducing blood cholesterol levels.
Many antihypercholesterolemic agents are presently used to cure cardiopathy disease and one of the best-known antihypercholesterolemic agents is pravastatin, which is prepared from modifying compactin, the only precursor of pravastatin. Thus, a process that can prepare compactin at a high concentration level is urgently required.
Compactin was first purified from the nutrient medium of Penicillium brevicocompactum and found to be an antifugal metabolite, as disclosed by Brown et al in 1975. Later, Endo et al in Japan Sankyo Company found that compactin exists in the fermentation broth of Penicillium citrinum. They also discovered compactin has blood cholesterol reducing ability.
U.S. Pat. No. 3,983,140 (Sep. 28, 1976) and U.S. Pat. No. 4,049,495 (Sep. 20, 1977) patented by A. Endo et al disclosed fermentative preparation of compactin by cultivation of a microorganism belonging to Penicillium citrinum.
U.S. Pat. No. 5,691,173 (Nov. 25, 1997) patented by Scott Primrose et al disclosed the preparation of compactin by fermentation using a microorganism belonging to Penicillium adametzoides.
In prior patents, compactin is prepared at an extremely low concentration level. Therefore, a novel microorganism or a new preparation is required to produce compactin at a high concentration level.